INTERACTION OF THE TRICYCLIC ANTI-DEPRESSANT AMITRIPTYLINE WITH PREJUNCTIONAL ALPHA-RECEPTORS AND MUSCARINIC RECEPTORS IN THE DOG SAPHENOUS-VEIN

  • 1 January 1980
    • journal article
    • research article
    • Vol. 213  (3) , 616-622
Abstract
Amitriptyline can cause tachycardia and arrhythmia associated with an excessive release of cardiac catecholamines. Its effects on norepinephrine [NE] release from adrenergic nerves was studied using the dog saphenous vein as a model of the sympathetic neuroeffector junction. Isolated strips of vein were mounted for isometric tension recording or incubated with [3H]NE and mounted for superfusion, tension recording and the determination of [3H]NE and its metabolites in the superfusate. Amitriptyline (10-6; 5 .times. 10-6 M) increased the overflow of [3H]NE but decreased that of [3,4-3H]dihydroxyphenylglycol from electrically stimulated strips. The selective decrease in the overflow of this metabolite indicates that amitriptyline inhibits neuronal uptake. The increased overflow of [3H]NE due to amitriptyline occurred when neuronal uptake was blocked by cocaine (3 .times. 10-5 M) but was abolished when prejunctional .alpha. receptors were blocked by phentolamine (10-5 M). Amitriptyline attenuated the prejunctional inhibitory action of exogenous NE, this indicates that the drug interacts with prejunctional .alpha. receptors. Amitriptyline antagonized the prejunctional inhibitory action of acetylcholine, both in the absence and presence of cocaine and phentolamine. These effects were not due to a nonspecific action of the drug as it did not reduce the prejunctional inhibitory effect of histamine. Amitriptyline can increase the concentration of NE at the neuroeffector junction by blockade of neuronal uptake and by interacting with prejunctional .alpha. and muscarinic receptors. Since the cardiac adrenergic nerves possess these receptors, the results could help to explain the cardiotoxic effects of the drug.